Unprecedented recent advances in biotechnology, immunology, and molecular biology have led to the development of new strategies for the treatment of rheumatic diseases. Some of these strategies are based on the use of monoclonal antibodies (mAb), which can inhibit selected cell subsets, surface molecules, or secreted products that promote pathologic immune responses. Other strategies are based on recombinant DNA technology, which has made it possible to construct analogues and/or inhibitors of distinct molecules that regulate inflammation and immunity. The long-term goal of this project is to rigorously test these strategies in people with rheumatic diseases. Realization of this goal will require a major change in direction for the principal investigator (PI) from basic research in animal models for autoimmune diseases to clinical study design and therapeutic trials in humans. This Development & Feasibility study consists of three specific objectives designed to accomplish this transition: 1) Formal training in clinical research. The PI will pursue a comprehensive program of training in clinical study design. This goal is realistic precisely because of the expertise that exists within the UCSF Multipurpose Arthritis Center. 2) Pilot study of anti-CD4 in systemic lupus erythematosus (SLE). We will perform a pilot study of the effects of mAb to CD4 in patients with SLE. This study is based on extensive animal research indicating that anti-CD4 can suppress autoimmunity in murine models for several important human autoimmune diseases. It will focus on the pharmacodynamics, toxicity, and immunogenicity of mAb to CD4. Moreover, it will serve as a training vehicle, and it will lay the foundation for subsequent controlled trials to determine the efficacy of anti-CD4 in people with SLE. 3) Controlled trial of anti-CD4 in SLE. Based on the information and expertise gained in pursuit of the first two goals, we will design and initiate a multicenter controlled trial comparing anti-CD4 with intravenous cyclophosphamide in patients with lupus nephritis.